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Blood, 1 July 2007, Vol. 110, No. 1, pp. 99-106.
Prepublished online as a Blood First Edition Paper on March 16, 2007; DOI 10.1182/blood-2006-11-059204.


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HEMATOPOIESIS

The zebrafish udu gene encodes a novel nuclear factor and is essential for primitive erythroid cell development

Yanmei Liu1,2, Linsen Du2, Motomi Osato3, Eng Hui Teo1, Feng Qian1,2, Hao Jin1,2, Fenghua Zhen1,2, Jin Xu1,2, Lin Guo2,4, Honghui Huang2,4, Jun Chen4, Robert Geisler5, Yun-Jin Jiang6, Jinrong Peng2,4, and Zilong Wen1,2

1 Laboratory of Molecular & Developmental Immunology, Institute of Molecular and Cell Biology, Proteos, Singapore; 2 Department of Biological Sciences, the National University of Singapore, Singapore; 3 Laboratory of Molecular Oncology, Institute of Molecular and Cell Biology, Proteos, Singapore; 4 Functional Genomics Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore; 5 Max Planck Institute fuer Entwicklungsbiologie, Tuebingen, Germany; 6 Laboratory of Developmental Signalling & Patterning, Institute of Molecular and Cell Biology, Proteos, Singapore

Hematopoiesis is a complex process which gives rise to all blood lineages in the course of an organism's lifespan. However, the underlying molecular mechanism governing this process is not fully understood. Here we report the isolation and detailed study of a newly identified zebrafish ugly duckling (Udu) mutant allele, Udusq1. We show that loss-of-function mutation in the udu gene disrupts primitive erythroid cell proliferation and differentiation in a cell-autonomous manner, resulting in red blood cell (RBC) hypoplasia. Positional cloning reveals that the Udu gene encodes a novel factor that contains 2 paired amphipathic {alpha}-helix–like (PAH-L) repeats and a putative SANT-L (SW13, ADA2, N-Cor, and TFIIIB–like) domain. We further show that the Udu protein is predominantly localized in the nucleus and deletion of the putative SANT-L domain abolishes its function. Our study indicates that the Udu protein is very likely to function as a transcription modulator essential for the proliferation and differentiation of erythroid lineage.


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